A spotlight on application of microwave-assisted modifications of plant derived polymers in designing novel drug delivery systems.

Polymers are a fundamental part of numerous industries and can be conjugated with many other materials and components to have a vast array of products. Biomaterials have been extensively studied for their application in pharmaceutical formulation development, tissue engineering, and biomedical areas. However, the native form of many polymers has limitations concerning microbial contamination, susceptibility, solubility, and stability. Chemical or physical modifications can overcome these limitations by tailoring the properties of polymers to meet several requirements. The polymer modifications are interdisciplinary, cutting across conventional materials, physics, biology, chemistry, medicine, and engineering limitations. Microwave irradiation has become a well-established technique for a few decades to drive and promote chemical modification reactions. This technique allows ease of temperature and power control to perform the synthesis protocols efficiently. Additionally, microwave irradiation contributes to green and sustainable chemistry. In this contribution, microwave-assisted polymer modifications were described with a special focus on their application in developing several novel dosage forms.

Computational Design, Synthesis, and Pharmacological Evaluation of Naproxen-Guaiacol Chimera for Gastro-Sparing Anti-Inflammatory Response by Selective COX2 Inhibition.

The 4-allyl guaiacol is a natural phenolic molecule that has been widely studied for its antioxidant capacity against reactive-oxygen-species-mediated cellular damage. Therefore, we hypothesized that concomitant use of an antioxidant and NSAID may decrease the risk of gastrointestinal toxicity and make the therapy safer. To address the gastrointestinal toxicity of conventional NSAIDs, a new S-naproxen-4-allyl guaiacol chimera (MAS-1696) was computationally developed, chemically synthesized, and tested for anti-inflammatory effectiveness and gastrointestinal safety. The inhibitory potency of MAS-1696 tested against cyclooxygenase-2 (COX2), 15-lipoxygenase-2 (15-LOX2), and lipoxygenase-5 (5-LOX) in vitro revealed a stronger inhibition of COX2. Furthermore, the MAS-1696 chimera increased the COX selectivity index by 23% as compared to the parent compound naproxen, implying higher efficacy and gastric safety. In vivo data showed that MAS-1696 was less likely to cause gastrointestinal harm than naproxen while also exerting anti-inflammatory and analgesic effects equivalent to or superior to naproxen. In conclusion, MAS-1696 is orally active, bio-labile, and crystalline, making it a medication that may be administered orally.

Green Synthesis and Characterization of Silver Nanoparticles of Psidium guajava Leaf Extract and Evaluation for Its Antidiabetic Activity.

Diabetes mellitus (DM) and its complications are a severe public health concern due to the high incidence, morbidity, and mortality rates. The present study aims to synthesize and characterize silver nanoparticles (AgNPs) using the aqueous leaf extract of Psidium guajava (PGE) for investigating its antidiabetic activity. Psidium guajava silver nanoparticles (PGAg NPs) were prepared and characterized by various parameters. The in vivo study was conducted using PGE and PGAg NPs in Streptozotocin (STZ)-induced diabetic rats to assess their antidiabetic properties. STZ of 55 mg/kg was injected to induce diabetes. The PGE, PGAg NPs at a dose of 200 and 400 mg/kg and standard drug Metformin (100 mg/kg) were administered daily to diabetic rats for 21 days through the oral route. Blood glucose level, body weight changes, lipid profiles, and histopathology of the rats' liver and pancreas were examined. In the diabetic rats, PGE and PGAg NPs produced a drastic decrease in the blood glucose level, preventing subsequent weight loss and ameliorating lipid profile parameters. The histopathological findings revealed the improvements in pancreas and liver cells due to the repercussion of PGE and PGAg NPs. A compelling effect was observed in all doses of PGE and PGAg NPs; however, PGAg NPs exhibited a more promising result. Thus, from the results, it is concluded that the synthesized PGAg NPs has potent antidiabetic activity due to its enhanced surface area and smaller particle size of nanoparticles.

Camel Proteins and Enzymes: A Growing Resource for Functional Evolution and Environmental Adaptation.

In less agroecological parts of the Asian, Arabian, and African deserts, Camelus dromedarius play an important role in human survival. For many years, camels have been employed as a source of food, a tool of transportation, and a means of defense. They are becoming increasingly important as viable livestock animals in many desert climates. With the help of camel genetics, genomics and proteomics known so far, this review article will summarize camel enzymes and proteins, which allow them to thrive under varied harsh environmental situations. An in-depth study of the dromedary genome revealed the existence of protein-coding and fast-developing genes that govern a variety of metabolic responses including lipid and protein metabolism, glucoamylase, flavin-containing monooxygenase and guanidinoacetate methyltransferase are other metabolic enzymes found in the small intestine, liver, pancreas, and spleen. In addition, we will discuss the handling of common medications by camel liver cytochrome p 450, which are different from human enzymes. Moreover, camels developed several paths to get optimum levels of trace elements like copper, zinc, selenium, etc., which have key importance in their body for normal regulation of metabolic events. Insulin tolerance, carbohydrate and energy metabolism, xenobiotics metabolizing enzymes, vimentin functions, behavior during the rutting season, resistance to starvation and changes in blood composition and resistance to water loss were among the attractive aspects of camel enzymes and proteins peculiarities in the camels. Resolving the enigma of the method of adaptation and the molecular processes linked with camel life is still a developing repository full of mysteries that need additional exploration.

The Race to Replace PDE5i: Recent Advances and Interventions to Treat or Manage Erectile Dysfunction: Evidence from Patent Landscape (2016-2021).

For a few decades, globally, erectile dysfunction (ED) has become more prominent even in young adults and represents a mounting health concern causing a significant effect on men's quality of life. There is an expectation that by the end of 2025, the number of ED cases can rise to 322 million. We aimed to comprehensively analyze the scientific output of scholarly articles and studies in the field of ED (2016-2021). Data from scholarly articles were collected using Pubmed, and clinical trials-related information was accessed from the clinical trials website. An extensive patent search was conducted using databases such as USPTO (United States patent and trademark office) and EPO (European patent office), WIPO (World Intellectual Property Organization), etc. Owing to the high market value of ED drugs, considerable interest was attained to grab the opportunities. The race to replace the phosphodiesterase type 5 inhibitor (PDE5 inhibitor-PDE5i) can be identified as evident from the significant number of patents filed and the inventions cleared with clinical trials. Some other intriguing interventions are identified for ED treatment but have yet to gain public acceptance. The current analysis confirms the overall evolution and unexplored corners of research on ED treatment strategies with a current global projection.

Nanomaterials in Dentistry: Current Applications and Future Scope.

Nanotechnology utilizes the mechanics to control the size and morphology of the particles in the required nano range for accomplishing the intended purposes. There was a time when it was predominantly applied only to the fields of matter physics or chemical engineering, but with time, biological scientists recognized its vast benefits and explored the advantages in their respective fields. This extension of nanotechnology in the field of dentistry is termed 'Nanodentistry.' It is revolutionizing every aspect of dentistry. It consists of therapeutic and diagnostic tools and supportive aids to maintain oral hygiene with the help of nanomaterials. Research in nanodentistry is evolving holistically but slowly with the advanced finding of symbiotic use of novel polymers, natural polymers, metals, minerals, and drugs. These materials, in association with nanotechnology, further assist in exploring the usage of nano dental adducts in prosthodontic, regeneration, orthodontic, etc. Moreover, drug release cargo abilities of the nano dental adduct provide an extra edge to dentistry over their conventional counterparts. Nano dentistry has expanded to every single branch of dentistry. In the present review, we will present a holistic view of the recent advances in the field of nanodentistry. The later part of the review compiled the ethical and regulatory challenges in the commercialization of the nanodentistry. This review tracks the advancement in nano dentistry in different but important domains of dentistry.

Progress Report: Antimicrobial Drug Discovery in the Resistance Era.

Antibiotic resistance continues to be a most serious threat to public health. This situation demands that the scientific community increase their efforts for the discovery of alternative strategies to circumvent the problems associated with conventional small molecule therapeutics. The Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report (published in June 2021) discloses the rapidly increasing number of bacterial infections that are mainly caused by antimicrobial-resistant bacteria. These concerns have initiated various government agencies and other organizations to educate the public regarding the appropriate use of antibiotics. This review discusses a brief highlight on the timeline of antimicrobial drug discovery with a special emphasis on the historical development of antimicrobial resistance. In addition, new antimicrobial targets and approaches, recent developments in drug screening, design, and delivery were covered. This review also discusses the emergence and roles of various antibiotic adjuvants and combination therapies while shedding light on current challenges and future perspectives. Overall, the emergence of resistant microbial strains has challenged drug discovery but their efforts to develop alternative technologies such as nanomaterials seem to be promising for the future.

Topical Probiotics: More Than a Skin Deep.

Skin, an exterior interface of the human body is home to commensal microbiota and also acts a physical barrier that protects from invasion of foreign pathogenic microorganisms. In recent years, interest has significantly expanded beyond the gut microbiome to include the skin microbiome and its influence in managing several skin disorders. Probiotics play a major role in maintaining human health and disease prevention. Topical probiotics have demonstrated beneficial effects for the treatment of certain inflammatory skin diseases such as acne, rosacea, psoriasis etc., and also found to have a promising role in wound healing. In this review, we discuss recent insights into applications of topical probiotics and their influence on health and diseases of the skin. Patents, commercially available topical probiotics, and novel probiotic impregnated fabrics have been emphasized. A thorough understanding of the relationship between probiotics and the skin microbiome is important for designing novel therapeutic approaches in using topical probiotics.

Optimized Rivastigmine Nanoparticles Coated with Eudragit for Intranasal Application to Brain Delivery: Evaluation and Nasal Ciliotoxicity Studies.

Rivastigmine, a reversible cholinesterase inhibitor, is frequently indicated in the management of demented conditions associated with Alzheimer disease. The major hurdle of delivering this drug through the oral route is its poor bioavailability, which prompted the development of novel delivery approaches for improved efficacy. Due to numerous beneficial properties associated with nanocarriers in the drug delivery system, rivastigmine nanoparticles were fabricated to be administer through the intranasal route. During the development of the nanoparticles, preliminary optimization of processing and formulation parameters was done by the design of an experimental approach. The drug-polymer ratio, stirrer speed, and crosslinking time were fixed as independent variables, to analyze the effect on the entrapment efficiency (% EE) and in vitro drug release of the drug. The formulation (D8) obtained from 23 full factorial designs was further coated using Eudragit EPO to extend the release pattern of the entrapped drug. Furthermore, the 1:1 ratio of core to polymer depicted spherical particle size of ~175 nm, % EE of 64.83%, 97.59% cumulative drug release, and higher flux (40.39 ± 3.52 µg.h/cm2). Finally, the intranasal ciliotoxicity study on sheep nasal mucosa revealed that the exposure of developed nanoparticles was similar to the negative control group, while destruction of normal architecture was noticed in the positive control test group. Overall, from the in vitro results it could be summarized that the optimization of nanoparticles' formulation of rivastigmine for intranasal application would be retained at the application site for a prolonged duration to release the entrapped drug without producing any local toxicity at the mucosal region.

Potential Interaction of Fresh Garlic with Metformin during Ischemia-Reperfusion Induced Cardiac Injury in Diabetic Rats.

METHODS: The study was undertaken on both normoglycemic and alloxan (90 mg/kg) induced diabetic Sprague Dawley rats weighing 150-250 g. At the completion of the treatment phase (30 days for garlic, 250 mg/kg, oral; 10 days for MET, 70 mg/kg, oral), rats were anesthetized and mounted on the modified Langendorff's apparatus. IRI was produced by myocardial no-flow global ischemia. Developed tension (DT) and heart rate (HR) were recorded both before and after ischemia. The perfusate was collected to estimate the leakage of cardiac biomarkers (Creatine Kinase-MB: CK-MB and Lactate dehydrogenase: LDH). Hearts were removed from the setup and utilized to prepare heart tissue homogenate (HTH) and histological slides. The endogenous antioxidants, superoxide dismutase (SOD) and catalase (CAT), in addition to oxidative thiobarbituric acid substances (TBS), were estimated in HTH. RESULTS: The hemodynamic parameters, including percentage recovery in HR and DT, were found significantly higher in animals pretreated with garlic and MET in diabetic rats (DR). Both SOD and CAT enzyme activities increased significantly while TBS levels were reduced in the HTH of animals treated with garlic and MET. The cardiac markers CK-MB and LDH levels also increased in HTH with a corresponding decrease in the perfusate. The histopathological changes in the heart and pancreas demonstrated noticeable protection of the tissues due to pretreatment with garlic and MET. Taken together, these findings advocate that reactive oxygen species derived from hyperglycemia execute an important function in myocardial global IRI; the therapy of garlic homogenate was found to be effective in alleviating these toxic effects. CONCLUSION: The combined therapy of MET and garlic provided synergistic cardioprotection, implying that garlic seems to possess promise in lowering toxic parameters by protecting diabetic induced myocardial injury.

Ion-Triggered In Situ Gelling Nanoemulgel as a Platform for Nose-to-Brain Delivery of Small Lipophilic Molecules.

Background: Intranasal route offers a direct nose-to-brain delivery via olfactory and trigeminal nerves and minimizes the systemic exposure of the drug. Although reliable and non-invasive, intranasal administration of lipophilic neuroprotective agents for brain targeting is still challenging. Literature focuses on naturally-derived compounds as a promising therapeutics for chronic brain diseases. Naringin, a natural flavonoid obtained from citrus fruits possesses neuroprotective effects. By regulating multiple crucial cellular signaling pathways, naringin acts on several therapeutic targets that make it suitable for the treatment of neurodegenerative diseases like Alzheimer's disease and making it a suitable candidate for nasal administration. However, the hydrophobicity of naringin is the primary challenge to formulate it in an aqueous system for nasal administration. Method: We designed a lipid-based nanoemulsifying drug delivery system of naringin using Acrysol K140 as an oil, Tween 80 as a surfactant and Transcutol HP as a cosolvent, to improve solubility and harness the benefits of nanosizing like improved cellular penetration. Intranasal instillations of therapeutic agents have limited efficacy due to drug washout and inadequate adherence to the nasal mucosa. Therefore, we reconstituted the naringin self-emulsifying system in a smart, biodegradable, ion-triggered in situ gelling hydrogel and optimized for desirable gel characteristics. The naringin-loaded composition was optimized and characterized for various physicochemical and rheological properties. Results: The formulation showed a mean droplet size 152.03 ± 4.6 nm with a polydispersity index <0.23. Ex vivo transmucosal permeation kinetics of the developed formulation through sheep nasal mucosa showed sustained diffusion and enhanced steady-state flux and permeability coefficient. Scanning and transmission electron microscopy revealed the spherical shape of emulsion droplets and entrapment of droplets in a gel structure. The formulation showed excellent biocompatibility as analyzed from the viability of L929 fibroblast cells and nasal mucosa histopathology after treatment. In vivo biodistribution studies revealed significantly higher drug transport and brain targeting efficiency. Conclusion: In situ gelling system with nanoemulsified naringin demonstrated a safe nasal delivery providing a new dimension to the treatment of chronic neurodegenerative diseases using small hydrophobic phytoconstituents with minimization of dose and related systemic adverse effects.

Nanotechnology Integration for SARS-CoV-2 Diagnosis and Treatment: An Approach to Preventing Pandemic.

The SARS-CoV-2 outbreak is the COVID-19 disease, which has caused massive health devastation, prompting the World Health Organization to declare a worldwide health emergency. The corona virus infected millions of people worldwide, and many died as a result of a lack of particular medications. The current emergency necessitates extensive therapy in order to stop the spread of the coronavirus. There are various vaccinations available, but no validated COVID-19 treatments. Since its outbreak, many therapeutics have been tested, including the use of repurposed medications, nucleoside inhibitors, protease inhibitors, broad spectrum antivirals, convalescence plasma therapies, immune-modulators, and monoclonal antibodies. However, these approaches have not yielded any outcomes and are mostly used to alleviate symptoms associated with potentially fatal adverse drug reactions. Nanoparticles, on the other hand, may prove to be an effective treatment for COVID-19. They can be designed to boost the efficacy of currently available antiviral medications or to trigger a rapid immune response against COVID-19. In the last decade, there has been significant progress in nanotechnology. This review focuses on the virus's basic structure, pathogenesis, and current treatment options for COVID-19. This study addresses nanotechnology and its applications in diagnosis, prevention, treatment, and targeted vaccine delivery, laying the groundwork for a successful pandemic fight.

Topical Nanoemulgel for the Treatment of Skin Cancer: Proof-of-Technology.

The present study is a mechanistic validation of 'proof-of-technology' for the effective topical delivery of chrysin nanoemulgel for localized, efficient treatment of melanoma-affected skin. BACKGROUND: Currently available treatments for skin cancer are inefficient due to systemic side effects and poor transcutaneous permeation, thereby presenting a formidable challenge for the development of novel nanocarriers. METHODS: We opted for a novel approach and formulated a nanocomplex system composed of hydrophobic chrysin dissolved in a lipid mix, which was further nanoemulsified in Pluronic® F-127 gel to enhance physicochemical and biopharmaceutic characteristics. Chrysin, a flavone extracted from passion flowers, exhibits potential anti-cancer activities; however, it has limited applicability due to its poor solubility. Pseudo-ternary phase diagrams were constructed to identify the best self-nanoemulsifying region by varying the compositions of oil, Caproyl® 90 surfactant, Tween® 80, and co-solvent Transcutol® HP. Chrysin-loaded nanoemulsifying compositions were characterized for various physicochemical properties. RESULTS: This thermodynamically stable, self-emulsifying drug delivery system showed a mean droplet size of 156.9 nm, polydispersity index of 0.26, and viscosity of 9100 cps after dispersion in gel. Mechanical characterization using Texture Analyzer exhibited that the gel had a hardness of 487 g and adhesiveness of 500 g. Ex vivo permeation through rat abdominal skin revealed significant improvement in percutaneous absorption measured as flux, the apparent permeability coefficient, the steady-state diffusion coefficient, and drug deposition. In vitro cytotoxicity on A375 and SK-MEL-2 cell lines showed a significantly improved therapeutic effect, thus ensuring reduction in dose. The safety of the product was established through biocompatibility testing on the L929 cell line. CONCLUSION: Aqueous, gel-based, topical, nanoemulsified chrysin is a promising technology approach for effective localized transcutaneous delivery that will help reduce the frequency and overall dose usage and ultimately improve the therapeutic index.

Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation.

BACKGROUND: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of resistance of microbes to existing drugs creates the need for the development of new effective antimicrobial agents. In an attempt to improve the antibacterial activity of previously synthesized compounds modifications to their structures were performed. METHODS: Nineteen thiazolidinone derivatives with 6-Cl, 4-OMe, 6-CN, 6-adamantan, 4-Me, 6-adamantan substituents at benzothiazole ring were synthesized and evaluated against panel of four bacterial strains S. aureus, L. monocytogenes, E. coli and S. typhimirium and three resistant strains MRSA, E. coli and P. aeruginosa in order to improve activity of previously evaluated 6-OCF3-benzothiazole-based thiazolidinones. The evaluation of minimum inhibitory and minimum bactericidal concentration was determined by microdilution method. As reference compounds ampicillin and streptomycin were used. RESULTS: All compounds showed antibacterial activity with MIC in range of 0.12-0.75 mg/mL and MBC at 0.25->1.00 mg/mL The most active compound among all tested appeared to be compound 18, with MIC at 0.10 mg/mL and MBC at 0.12 mg/mL against P. aeruginosa. as well as against resistant strain P. aeruginosa with MIC at 0.06 mg/mL and MBC at 0.12 mg/mL almost equipotent with streptomycin and better than ampicillin. Docking studies predicted that the inhibition of LD-carboxypeptidase is probably the possible mechanism of antibacterial activity of tested compounds. CONCLUSION: The best improvement of antibacterial activity after modifications was achieved by replacement of 6-OCF3 substituent in benzothiazole moiety by 6-Cl against S. aureus, MRSA and resistant strain of E. coli by 2.5 folds, while against L. monocytogenes and S. typhimirium from 4 to 5 folds.

COVID-19 and Psychological Health of Female Saudi Arabian Population: A Cross-Sectional Study.

The influence of the COVID-19 pandemic is unprecedented on physical and mental health. This study aimed to determine the impact of the COVID-19 event on mental health among Saudi Arabian females of Riyadh by a cross-sectional study design. The samples of the study were recruited using convenience and snowball sampling methods. The questionnaire is composed of items related to sociodemographic profile, general mental status, negative attitude scale, impact of event (COVID-19 pandemic) scale (R) and negative health impact. The data obtained were analyzed using multivariate regression analysis. Out of the 797 samples (34.58 ± 12.89 years), 457 (57.34%) belonged to an age group of ≥25 years. The average BMI of the participants was 26.73 (kg/m2). Significantly (p = 0.000), a large proportion of the participants were overweight and unemployed. Age group (>25 years) have more odds for abnormal mental status (OR; 1.592), development of negative attitudes (OR; 1.986), the intense impact of COVID-19 events (OR; 1.444) and susceptibility to attain negative health impacts (OR; 1.574). High body weight is another risk factor for altered mental status, negative attitude and developing impact of COVID-19 quickly. Overall, the COVID-19 pandemic was directly associated with stress (53%), anxiety (63%) and depression (44%) in our sample population. There is an urgent need for psychological counseling for the distressed population.

Role of Daucus carota in Enhancing Antiulcer Profile of Pantoprazole in Experimental Animals.

The carrot plant (Daucus carota) and its components are traditionally reported for the management of gastric ulcers. This study was performed to evaluate the role of carrot when administered concurrently with a conventional antiulcer treatment, pantoprazole, in alleviating gastric and duodenal ulcers in female experimental animals. The study involved standard animal models to determine the ulcer preventive effect using pylorus ligation, ethanol, and stress induced acute gastric ulcer models and duodenal ulcer models involving cysteamine. Acetic acid-induced chronic gastric ulcer and indomethacin-induced gastric ulcer models were used to evaluate the ulcer healing effect. Carrot fruit (500 mg/kg) and its co-administration with pantoprazole produced significant protection in an ethanol- and stress-induced acute gastric ulcer and cysteamine-induced duodenal ulcer. The healing of the acetic acid-induced chronic gastric ulcer was also augmented with this combination. Both total proteins and mucin contents were significantly increased in indomethacin-induced gastric ulcers. Similarly, in pylorus ligation, the pepsin content of gastric juice, total acidity, and free acidity were reduced. Overall, both ulcer preventive effects and ulcer healing properties of the pantoprazole were significantly enhanced in animals who received the co-administration of carrot fruit (500 mg/kg).

Pathophysiology of high fat diet induced obesity: impact of probiotic banana juice on obesity associated complications and hepatosteatosis.

The high fat diet alters intestinal microbiota due to increased intestinal permeability and susceptibility to microbial antigens leads to metabolic endotoxemia. But probiotic juices reported for various health benefits. In this background we hypothesized that pectinase treated probiotic banana juice has diverse effects on HFD induced obesity and non-alcoholic steatohepatitis. 20 weeks fed HFD successfully induced obesity and its associated complications in experimental rats. The supplementation of probiotic banana juice for 5 months at a dose of 5 mL/kg bw/day resulted significant decrease (p < 0.05) in body weight (380 ± 0.34), total fat (72 ± 0.8), fat percentage (17 ± 0.07) and fat free mass (165 ± 0.02). Reduction (p < 0.05) in insulin resistance (5.20 ± 0.03), lipid profile (TC 120 ± 0.05; TG 160 ± 0.24; HDL 38 ± 0.03), liver lipid peroxidation (0.7 ± 0.01), hepatic enzyme markers (AST 82 ± 0.06; ALT 78 ± 0.34; ALP 42 ± 0.22), and hepatic steatosis by increasing liver antioxidant potential (CAT 1.4 ± 0.30; GSH 1.04 ± 0.04; SOD 0.82 ± 0.22) with normal hepatic triglycerides (15 ± 0.02) and glycogen (0.022 ± 0.15) contents and also showed normal liver size, less accumulation of lipid droplets with only a few congestion. It is concluded that the increased intestinal S. cerevisiae yeast can switch anti-obesity, antidiabetic, antioxidative stress, antioxidant and anti-hepatosteatosis effect. This study results will have significant implications for treatment of NAFLD.